Leukotriene D4 contractions in human airways are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry.
In human bronchial muscle preparations, nifedipine (3 microM) significantly inhibited the histamine, ACh and KCl contractions. However, the dihydropyridine did not modify the contractile responses induced by either leukotriene D4 (LTD4) or anti-human IgE (a-IgE). In human airways, SK&F 96365 (30 microM and 100 microM) markedly reduced the KCl and, at the higher concentration, LTD4 maximal contractions. In addition, when preparations were treated with nifedipine (3 microM), SK&F 96365 (100 microM) significantly blocked responses to both LTD4 and a-IgE. The calcium chelating agent ethylene glycol-bis (beta-amino-ethyl ether) N,N,N',N'-tetraacetic acid (4 mM) also inhibited the a-IgE-induced contractions. These data demonstrate that the nifedipine-resistant component of the LTD4 and a-IgE contractions was inhibited by SK&F 96365 and suggest that the cysteinyl-leukotriene receptor in human airways may be intimately linked with a receptor-operated calcium-entry mechanism.
Gorenne
I
I
CNRS ERS 566 Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
Labat
C
C
Gascard
J P
JP
Norel
X
X
Nashashibi
N
N
Brink
C
C
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D017998:Leukotriene D4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D002121:Calcium Channel Blockers; D007093:Imidazoles; D007073:Immunoglobulin E; D017998:Leukotriene D4; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium